title: Antiproliferative activity of Rhinella marina and Rhaebo guttatus venom extracts from Southern Amazon.
abstract: The venom of amphibians is a fascinating source of active substances. In view of their medical importance and aiming to explore the amazing Brazilian biodiversity, we conducted bioprospecting of antiproliferative activity in extracts of Rhinella marina and Rhaebo guttatus toads occurring in the Southern Amazon of Mato Grosso, Brazil. LC-MS and HPLC analysis of the venom extracts of R. marina revealed four bufadienolides (telocinobufagin, marinobufagin, bufalin and resibufogenin. R. guttatus venom extracts contained only marinobufagin. First, R. marina and R. guttatus venom extracts were evaluated for cytotoxicity against tumor cell lines by the MTT assay. All extracts revealed cytotoxicity, where R. marina extracts were comparable to doxorubicin (IC₅₀ values ranging from 0.01 to 0.23 μg/mL). Only extracts of R. guttatus toad venom caused membrane disruption of human erythrocytes. The extracts were investigated for selective activity by determining their effect on stimulated human peripheral blood mononuclear cells (PBMC) with the Alamar Blue™ assay. The extracts were up to 80-fold more selective against leukemia cells when compared to dividing leukocytes. Aiming to confirm these antiproliferative effects, BrdU incorporation into DNA was measured in HL-60 treated cells with R. marina venom extracts. These extracts decreased BrdU incorporation at both concentrations tested. In summary, nine extracts of R. marina and R. guttatus venom showed pronounced lethal and discriminating effects on tumor lines, especially those from R. marina, highlighting toad parotoid gland secretions as a promising source for novel lead anticancer chemicals.
authors.affiliation: Department of Biological Sciences, Campus Senador Helvídio Nunes de Barros, Federal University of Piauí, 64607-670 Picos, Piauí, Brazil.
authors.forename: Paulo Michel Pinheiro
authors.initials: PM
authors.lastname: Ferreira
authors.forename: Daisy Jereissati Barbosa
authors.initials: DJ
authors.lastname: Lima
authors.forename: Bryan Wender
authors.initials: BW
authors.lastname: Debiasi
authors.forename: Bruno Marques
authors.initials: BM
authors.lastname: Soares
authors.forename: Kátia da Conceição
authors.initials: Kda C
authors.lastname: Machado
authors.forename: Janaina da Costa
authors.initials: Jda C
authors.lastname: Noronha
authors.forename: Domingos de Jesus
authors.initials: Dde J
authors.lastname: Rodrigues
authors.forename: Adilson Paulo
authors.initials: AP
authors.lastname: Sinhorin
authors.forename: Cláudia
authors.initials: C
authors.lastname: Pessoa
authors.forename: Gerardo Magela
authors.initials: GM
authors.lastname: Vieira
mesh_terms: D000664:Amphibian Venoms / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001938:Brazil; D002025:Bufonidae; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects
chemical_list: D000664:Amphibian Venoms; D054697:Cytostatic Agents
keywords: Antiproliferative activity; Bufadienolides; Rhaebo guttatus; Rhinella marina